Humans respond to infectious challenge by a stress response that results in the release of epinephrine. Epinephrine is beneficial in supporting the hyper-metabolism of fever by substrate mobilization and by increased cardiovascular function. The present application examines the stress response to infection and considers how the known mediators of the stress response may be controlled by immune cells. The long range goal is to therapeutically manipulate the stress response to infection, maximizing compensatory physiologic response and improving resistance to infection. Preliminary results: Epinephrine secretion from chromaffin cells can be caused by a 6 amino acid peptide which is produced by immune cells. The peptide: 1) has been isolated as a single band on polyacrylamide gel; 2) has a molecular weight of approximately 635 by mass spectrometry; 3) has bioactivity that can be blocked by an antibody; 4) may come from a parent peptide which also binds to an antibody; and 5) is produced primarily by T helper cells and endotoxin-stimulated macrophages. Specific Aim 1 is to identify and characterize the bioactive peptide from immune cells; 2 is to identify the specific mononuclear cell type that produces the peptide; and 3 is to determine the in vivo relevance of the peptide. Methods: Peptide isolation will proceed by gel filtration, gel electrophoresis, reverse phase and affinity chromatography, followed by amino acid analysis and sequencing. Mononuclear cells will be separated by standard techniques using antibodies. Conditioned media, purified peptide, or antibody to the peptide will be tested for effects on plasma epinephrine levels in whole animals. Significance: Identification of a previously unknown peptide linking immune and neuroendocrine function involved in the stress response to infection will have important therapeutic potential to manage whole-body responses to infectious challenge.